For many, prolonged attempts to become pregnant end in failure, resulting in their seeking assistance from an infertility clinic. Infertility can result from a great variety of causes, including anatomical, developmental, infectious and toxicological factors. Poor oocyte quality is the cause of infertility in a significant number of the 1.6 million American couples unable to conceive a child.
Various methods for assisted reproduction technology (ART) have been developed and used to assist couples unable to become pregnant naturally. Examples of ART include in vitro fertilization-embryo transfer (IVF-ET), intracytoplasmic sperm injection (ICSI), testicular sperm extraction (TESE), round spermatid injection (ROSI) and-embryo freezing. While ART is an important and general method for the treatment of sterile patients, there remain problems to be overcome, such as the low chance of success of becoming pregnant using ART.
In the United States, 15% of women of childbearing age have received an infertility treatment. There were 86,822 ART cycles reported in 1999, resulting in the birth of 30,285 babies (Assisted Reproductive Technology Success Rates National Summary and Fertility Clinic Reports. Centers for Disease Control/SART, Bethesda, Md., 1999). Thus, unfortunately, 69% of IVF cycles do not result in pregnancy. The woman's age appears as an important factor affecting the chance of live birth and risk of miscarriage when her own oocytes are used (See, e.g., Krisher, J. Anim. Sci., 82 (E Suppl) E14-E23 (2004)). Currently, about 10% of all ART cycles (9066 cycles in 1999) use donor oocytes. With her own oocytes, a 29-year old woman has about a 40% chance of achieveing pregnancy during an ART cycle. This figure drops to 32% by 36 years of age and nearly 0% by 46 years of age. However, when donor oocytes are used the chance of achieving pregnancy during ART stays around 40% regardless of the age of the patient. Thus, oocytes from older women are less competent, exemplifying the importance of oocyte quality (e.g., oocyte development potential) and the ability to characterize and/or determine the same.
As an oocyte grows and matures, it acquires the ability to resume and complete meiosis, successfully undergo the fertilization process, and initiate and sustain embryonic development. The mammalian oocyte and its surrounding somatic cells are interdependent throughout the growth and development of the oocyte and ovarian follicle of a female subject. Growing oocytes derive most substrates for energy metabolism and biosynthesis from granulosa cells. Cumulus cells are a sub-group of granulosa cells that surround the oocyte in an antral follicle and, because of their close proximity to the oocyte, play an important role in regulating oocyte maturation.
Abnormal patterns of gene expression in cumulus cells may lead to abnormal development of the oocyte (e.g., the inability of the oocyte to become fertilized), or the inability of the oocyte post fertilization (e.g., fertilized oocyte or embryo) to implant into the uterine wall of a female subject. What is needed are compositions and methods for understanding the regulation of oocyte growth and maturation. Specifically, compositions and methods are needed to determine oocyte development potential. Such compositions and methods may be able to provide markers for identifying the developmental potential of the oocyte and may provide compositions, methods and treatments useful for assisting normal oocyte development. For example, the ability to determine oocyte development potential could be used in the ART setting to identify oocytes possessing the highest probability of being fertilized and/or implanting within the uterus of a female subject, thereby decreasing costs associated with and increasing the probability of success using ARTs.